Chromosome 18q 22-23 has been linked to bipolar affective disorder (BPAD) in several studies. We have identified in our sample pedigrees that define a strongly linked 6 MB region on 18q22 with a lod score of 4.85. The Specific Aims of this research training proposal are to 1) Identify candidate genes in and around the BPAD linkage region on 18q22-23 by screening sequence data from the Human Genome Project; 2) To identify single nucleotide polymorphism markers (SNP?s) in and near these candidate genes in and near these candidate genes by mining the public databases and by re-sequencing PCR products in our laboratory; 3) To genotype selected SNP?s in 2-4 positional candidate genes using single base extension and other high throughput methods; 4) To test each gene for association with BPAD in a sample of 400 triads, using family based statistical methods. This project will offer me a complete experience in positional candidate gene research, forming the basis for my future career. Identification of the genes that predispose to BPAD would offer novel and powerful insights into the etiology and ultimately the treatment of BPAD.